Cancer Cell Membrane‐Biomimetic Oxygen Nanocarrier for Breaking Hypoxia‐Induced Chemoresistance

The inadequate oxygen supply in solid tumor causes hypoxia, which leads to drug resistance and poor chemotherapy outcomes. To solve this problem, a cancer cell membrane camouflaged nanocarrier is developed with a polymeric core encapsulating hemoglobin (Hb) and doxorubicin (DOX) for efficient chemotherapy. The designed nanoparticles (DHCNPs) retain the cancer cell adhesion molecules on the surface of nanoparticles for homologous targeting and possess the oxygen‐carrying capacity of Hb for O2‐interfered chemotherapy. The results show that DHCNPs not only achieve higher tumor specificity and lower toxicity by homologous targeting but also significantly reduce the exocytosis of DOX via suppressing the expressions of hypoxia‐inducible factor‐1α, multidrug resistance gene 1, and P‐glycoprotein, thus resulting in safe and high‐efficient chemotherapy. This work presents a new paradigm for targeted oxygen interference therapy by conquering hypoxia‐involved therapeutic resistance and achieves effective treatment of solid tumors. The biomimetic oxygen nanocarrier (DHCNPs), consisting of a doxorubicin (DOX)/Hb‐loaded polymeric core and cancer cell membrane shell, exhibits highly effective delivery of drug and oxygen to homologous cancer cells. Sufficient oxygen supply alters tumor hypoxia and consequently downregulates the expressions of hypoxia‐inducible factor‐1α, multidrug resistance gene 1, and P‐glycoprotein, resulting in inhibited DOX efflux and enhanced chemotherapy with intense intracellular DOX accumulation.